Hanks Sandra, Coleman Kim, Reid Sarah, Plaja Alberto, Firth Helen, Fitzpatrick David, Kidd Alexa, Méhes Károly, Nash Richard, Robin Nathanial, Shannon Nora, Tolmie John, Swansbury John, Irrthum Alexandre, Douglas Jenny, Rahman Nazneen
Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey, UK.
Nat Genet. 2004 Nov;36(11):1159-61. doi: 10.1038/ng1449. Epub 2004 Oct 10.
Mosaic variegated aneuploidy is a rare recessive condition characterized by growth retardation, microcephaly, childhood cancer and constitutional mosaicism for chromosomal gains and losses. In five families with mosaic variegated aneuploidy, including two with embryonal rhabdomyosarcoma, we identified truncating and missense mutations of BUB1B, which encodes BUBR1, a key protein in the mitotic spindle checkpoint. These data are the first to relate germline mutations in a spindle checkpoint gene with a human disorder and strongly support a causal link between aneuploidy and cancer development.
嵌合性杂合非整倍体是一种罕见的隐性疾病，其特征为生长发育迟缓、小头畸形、儿童期癌症以及染色体增减的体质性嵌合现象。在五个患有嵌合性杂合非整倍体的家族中，包括两个患有胚胎性横纹肌肉瘤的家族，我们鉴定出了BUB1B基因的截短突变和错义突变，该基因编码BUBR1，这是有丝分裂纺锤体检查点中的一种关键蛋白。这些数据首次将纺锤体检查点基因中的种系突变与一种人类疾病联系起来，并有力地支持了非整倍体与癌症发生之间的因果关系。
